tbuckley/cabot-search huggingface dataset:
New insights into human immune memory from <scp>SARS‐CoV</scp>‐2 infection and vaccination
Authors: Gemma E. Hartley, Emily S. J. Edwards, Robyn E. O’Hehir, Menno C. van Zelm
Journal: Allergy (2022)

Abstract Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and innovative means to identify infected individuals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected individuals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS‐CoV‐2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan‐based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants.
MIRTH: Metabolite Imputation via Rank-Transformation and Harmonization
Authors: Benjamin A. Freeman, Sophie Jaro, Tricia Park, Sam Keene, Wesley Tansey, Ed Reznik
Journal: Genome biology (2022)

Abstract Out of the thousands of metabolites in a given specimen, most metabolomics experiments measure only hundreds, with poor overlap across experimental platforms. Here, we describe Metabolite Imputation via Rank-Transformation and Harmonization (MIRTH), a method to impute unmeasured metabolite abundances by jointly modeling metabolite covariation across datasets which have heterogeneous coverage of metabolite features. MIRTH successfully recovers masked metabolite abundances both within single datasets and across multiple, independently-profiled datasets. MIRTH demonstrates that latent information about otherwise unmeasured metabolites is embedded within existing metabolomics data, and can be used to generate novel hypotheses and simplify existing metabolomic workflows.
Prediction of evolutionary constraint by genomic annotations improves functional prioritization of genomic variants in maize
Authors: Guillaume P. Ramstein, Edward S. Buckler
Journal: Genome biology (2022)

Crop improvement through cross-population genomic prediction and genome editing requires identification of causal variants at high resolution, within fewer than hundreds of base pairs. Most genetic mapping studies have generally lacked such resolution. In contrast, evolutionary approaches can detect genetic effects at high resolution, but they are limited by shifting selection, missing data, and low depth of multiple-sequence alignments. Here we use genomic annotations to accurately predict nucleotide conservation across angiosperms, as a proxy for fitness effect of mutations.Using only sequence analysis, we annotate nonsynonymous mutations in 25,824 maize gene models, with information from bioinformatics and deep learning. Our predictions are validated by experimental information: within-species conservation, chromatin accessibility, and gene expression. According to gene ontology and pathway enrichment analyses, predicted nucleotide conservation points to genes in central carbon metabolism. Importantly, it improves genomic prediction for fitness-related traits such as grain yield, in elite maize panels, by stringent prioritization of fewer than 1% of single-site variants.Our results suggest that predicting nucleotide conservation across angiosperms may effectively prioritize sites most likely to impact fitness-related traits in crops, without being limited by shifting selection, missing data, and low depth of multiple-sequence alignments. Our approach-Prediction of mutation Impact by Calibrated Nucleotide Conservation (PICNC)-could be useful to select polymorphisms for accurate genomic prediction, and candidate mutations for efficient base editing. The trained PICNC models and predicted nucleotide conservation at protein-coding SNPs in maize are publicly available in CyVerse ( https://doi.org/10.25739/hybz-2957 ).
Group 3 innate lymphoid cells require BATF to regulate gut homeostasis in mice
Authors: Xiaopeng Wu, Achia Khatun, Moujtaba Y. Kasmani, Yao Chen, Shikan Zheng, Samantha Atkinson, Christine Nguyen, Robert Burns, Elizabeth J. Taparowsky, Nita H. Salzman, Timothy W. Hand, Weiguo Cui
Journal: The Journal of Experimental Medicine (2022)

Group 3 innate lymphoid cells (ILC3s) are crucial for the maintenance of host-microbiota homeostasis in gastrointestinal mucosal tissues. The mechanisms that maintain lineage identity of intestinal ILC3s and ILC3-mediated orchestration of microbiota and mucosal T cell immunity are elusive. Here, we identified BATF as a gatekeeper of ILC3 homeostasis in the gut. Depletion of BATF in ILC3s resulted in excessive interferon-γ production, dysbiosis, aberrant T cell immune responses, and spontaneous inflammatory bowel disease (IBD), which was considerably ameliorated by the removal of adaptive immunity, interferon-γ blockade, or antibiotic treatment. Mechanistically, BATF directly binds to the cis-regulatory elements of type 1 effector genes, restrains their chromatin accessibility, and inhibits their expression. Conversely, BATF promotes chromatin accessibility of genes involved in MHCII antigen processing and presentation pathways, which in turn directly promotes the transition of precursor ILC3s to MHCII+ ILC3s. Collectively, our findings reveal that BATF is a key transcription factor for maintaining ILC3 stability and coordinating ILC3-mediated control of intestinal homeostasis.
CTCF and cohesin promote focal detachment of DNA from the nuclear lamina
Authors: Tom van Schaik, Ning Qing Liu, Stefano G. Manzo, Daan Peric-Hupkes, Elzo de Wit, Bas van Steensel
Journal: Genome biology (2022)

Abstract Background Lamina-associated domains (LADs) are large genomic regions that are positioned at the nuclear lamina. It has remained largely unclear what drives the positioning and demarcation of LADs. Because the insulator protein CTCF is enriched at LAD borders, it was postulated that CTCF binding could position some LAD boundaries, possibly through its function in stalling cohesin and hence preventing cohesin invading into the LAD. To test this, we mapped genome–nuclear lamina interactions in mouse embryonic stem cells after rapid depletion of CTCF and other perturbations of cohesin dynamics. Results CTCF and cohesin contribute to a sharp transition in lamina interactions at LAD borders, while LADs are maintained after depletion of these proteins, also at borders marked by CTCF. CTCF and cohesin may thus reinforce LAD borders, but do not position these. CTCF binding sites within LADs are locally detached from the lamina and enriched for accessible DNA and active histone modifications. Remarkably, despite lamina positioning being strongly correlated with genome inactivity, this DNA remains accessible after the local detachment is lost following CTCF depletion. At a chromosomal scale, cohesin depletion and cohesin stabilization by depletion of the unloading factor WAPL quantitatively affect lamina interactions, indicative of perturbed chromosomal positioning in the nucleus. Finally, while H3K27me3 is locally enriched at CTCF-marked LAD borders, we find no evidence for an interplay between CTCF and H3K27me3 on lamina interactions. Conclusions These findings illustrate that CTCF and cohesin are not primary determinants of LAD patterns. Rather, these proteins locally modulate NL interactions.
Tom Nolan’s research reviews—1 September 2022
Authors: Tom Nolan
Journal: BMJ (2022)

Remote ischaemic conditioning-an unlikely treatment for acute ischaemic strokeJAMA reports a promising new treatment for acute ischaemic stroke that falls in the categories of "I would never have thought that might work" and "don't try this at home."Remote ischaemic conditioning (RIC) involves "brief, reversible episodes of ischaemia and reperfusion in one vascular bed to activate ischaemia tolerance in remote tissues and organs."In practice, this means inflating a blood pressure cuff on both arms to 200 mm Hg for five minutes, deflating for five minutes, and repeating this cycle four more times, and doing the whole thing again twice a day for two weeks.The largest randomised trial of RIC to date recruited adults with acute moderate ischaemic stroke who had not received thrombolysis or endovascular therapy.The primary endpoint-excellent neurological function after 90 days-was seen slightly more in those receiving RIC (67.4% versus 62% of controls, odds ratio 1.27, P=0.02), but the findings from this open label study need to be replicated before RIC can be said to be an effective treatment for acute ischaemic stroke (JAMA
Broader Epstein–Barr virus–specific T cell receptor repertoire in patients with multiple sclerosis
Authors: Tilman Schneider-Hohendorf, Lisa Ann Gerdes, Béatrice Pignolet, Rachel Gittelman, Patrick Ostkamp, Florian Rubelt, Catarina Raposo, Björn Tackenberg, Marianne Riepenhausen, Claudia Janoschka, Christian Wünsch, Florence Bucciarelli, Andrea Flierl-Hecht, Eduardo Beltrán, Tania Kümpfel, Katja Anslinger, Catharina C. Gross, Heidi Chapman, Ian Kaplan, David Brassat, Hartmut Wekerle, Martin Kerschensteiner, Luisa Klotz, Jan D. Lünemann, Reinhard Hohlfeld, Roland Liblau, Heinz Wiendl, Nicholas Schwab
Journal: The Journal of Experimental Medicine (2022)

Epstein-Barr virus (EBV) infection precedes multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection to CNS autoimmunity. As an altered anti-EBV T cell reaction was suggested in MS, we queried peripheral blood T cell receptor β chain (TCRβ) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimer-confirmed, viral antigen-specific TCRβ sequences. We detected more MHC-I-restricted EBV-specific TCRβ sequences in MS patients. Differences in genetics or upbringing could be excluded by validation in monozygotic twin pairs discordant for MS. Anti-VLA-4 treatment amplified this observation, while interferon β- or anti-CD20 treatment did not modulate EBV-specific T cell occurrence. In healthy individuals, EBV-specific CD8+ T cells were of an effector-memory phenotype in peripheral blood and cerebrospinal fluid. In MS patients, cerebrospinal fluid also contained EBV-specific central-memory CD8+ T cells, suggesting recent priming. Therefore, MS is not only preceded by EBV infection, but also associated with broader EBV-specific TCR repertoires, consistent with an ongoing anti-EBV immune reaction in MS.
Precise gliomas therapy: Hypoxia-activated prodrugs sensitized by nano-photosensitizers
Authors: Han Zhang, Chao Shi, Fuping Han, Mengqi Li, He Ma, Rui Sui, Saran Long, Wen Sun, Jianjun Du, Jiangli Fan, Haozhe Piao, Xiaojun Peng
Journal: Biomaterials (2022)
The potential role of the mobile and non-coding genomes in adaptive response
Authors: Alice M. Godden, Simone Immler
Journal: Trends in Genetics (2022)

The tightly regulated feedback loops linking small RNAs (sRNAs) and transposable elements (TEs) offer the opportunity for an adaptive response to changing environments at the molecular level. Environmentally induced changes in TE and sRNA profiles may affect expression of coding genes and trigger an organismic and transgenerational response. Understanding this link may provide a mechanistic explanation for how species can adapt to changing climates and may offer novel molecular targets for biomedical and agricultural applications.
Tissue Niche Miniature of Glioblastoma Patient Treated with Nano‐Awakeners to Induce Suicide of Cancer Stem Cells
Authors: Seon‐Jin Yoon, Sewoom Baek, Seung Eun Yu, Euna Jo, Dongkyu Lee, Jin‐Kyoung Shim, Ran Joo Choi, Junseong Park, Ju Hyung Moon, Eui‐Hyun Kim, Jong Hee Chang, Jung Bok Lee, Joon‐Sang Park, Hak‐Joon Sung, Seok‐Gu Kang
Journal: Advanced Healthcare Materials (2022)

Patient-specific cancer therapies can evolve by vitalizing the mother tissue-like cancer niche, cellular profile, genetic signature, and drug responsiveness. This evolution has enabled the elucidation of a key mechanism along with development of the mechanism-driven therapy. After surgical treatment, glioblastoma (GBM) patients require prompt therapy within 14 days in a patient-specific manner. Hence, this study approaches direct culture of GBM patient tissue (1 mm diameter) in a microchannel network chip. Cancer vasculature-mimetic perfusion can support the preservation of the mother tissue-like characteristic signatures and microenvironment. When temozolomide and radiation are administered within 1 day, the responsiveness of the tissue in the chip reflected the clinical outcomes, thereby overcoming the time-consuming process of cell and organoid culture. When the tissue chip culture is continued, the intact GBM signature gets lost, and the outward migration of stem cells from the tissue origin increases, indicating a leaving-home effect on the family dismantle. Nanovesicle production using GBM stem cells enables self-chasing of the cells that escape the temozolomide effect owing to quiescence. The anti-PTPRZ1 peptide display and temozolomide loading to nanovesicles awakes cancer stem cells from the quiescent stage to death. This study suggests a GBM clinic-driven avatar platform and mechanism-learned nanotherapy for translation.
First Nerve‐Related Immunoprobe for Guidance of Renal Denervation through Colocalization of NIR‐II and Photoacoustic Bioimaging
Authors: Shi Yibing, Tang Minna, Zhang Sidi, Hu Chenchen, Li Cheng, Li Quanxiao, Huang Keke, Song Wenping, Li Zhixing, Li Wenshu, Yang Zhenlin, Wu Yanling, Li Fuyou, Hu Jialu, Ying Tianlei
Journal: Advanced Healthcare Materials (2022)

Abstract Nerve‐related fluorophores generally locate in the visible or near‐infrared region with shallow penetration depth and easy uptake by surrounding tissues. Prolonging the optical window promotes resolution by minimizing photoscattering and eliminating autofluorescence for NIR‐II (second near infrared; 1000–1700 nm) and photoacoustic bioimaging. In addition, combination of the two could help in colocalization of targets at the 3D level. Catheter‐based renal sympathetic denervation (RDN), an alternative treatment recently finishing its clinical evaluation for treating resistant hypertension, is highly dependent on experience and in urgent demand for in vivo guidance in locating the nerve over the renal artery. Here, an NIR‐II and photoacoustic bioimaging system based on a dye‐modified anti‐tyrosine‐hydroxylase antibody (TH‐ICGM) to illustrate the peritoneal sympathetic nerve‐related region are combined. With high resolution (0.15 mm) in NIR‐II region for both absorbance ( λ ex = 925 nm) and fluorescence (bioimaging in λ em ≥ 1300 nm), TH‐ICGM succeeds in providing 3D coordinates of procedure position with a precision in 0.1 mm. As the first nerve‐related NIR‐II immunoprobe, TH‐ICGM has great clinical potential as assistance for nerve‐related interventions.
Sputum transcriptome analysis of co‐regulated genes related to arachidonic acid metabolism in <scp>N‐ERD</scp>
Authors: Lucyna Mastalerz, Radosław Kacorzyk, Bogdan Jakieła, Adam Ćmiel, Marek Sanak
Journal: Allergy (2022)

Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Construction of Wogonin Nanoparticle‐Containing Strontium‐Doped Nanoporous Structure on Titanium Surface to Promote Osteoporosis Fracture Repair
Authors: Dong Wang, Mao‐Wen Chen, Yu‐Jia Wei, Wen‐Bo Geng, Yan Hu, Zhong Luo, Kai‐Yong Cai
Journal: Advanced Healthcare Materials (2022)

Abstract M2 polarization of macrophage is an important immunomodulatory event that attenuates inflammation. To regulate the immune microenvironment in osteoporotic conditions for enhancing bone healing, strontium‐doped nano‐structure is fabricated on the surface of titanium implant via microarc oxidation and electrochemical deposition technology, followed by the addition of multiplayer coatings embedded with silk fibroin‐based wogonin nanoparticles (Ti‐MAO/Sr/LBL WNP ) by layer‐by‐layer self‐assembly technique (LBL). It is found that Ti‐MAO/Sr/LBL WNP can release wogonin and Sr 2+ in a sustainable manner for more than 7 and 21 days. In vitro studies show that Ti‐MAO/Sr/LBL WNP significantly upregulates the expression of CD206 while reducing the expression of CD86. Meanwhile, Ti‐MAO/Sr/LBL WNP can promote the expression level of M2 macrophage anti‐inflammatory factor (TGF‐ β 1, Arg‐1), which improves the proliferation and osteogenic differentiation of osteoblasts through paracrine signaling. Compared to bare titanium, Ti‐MAO/Sr/LBL WNP significantly inhibits the expression of inflammatory factors around the implant and effectively promotes new bone formation at pre‐implant interface after implantation for 4 weeks. This study provides a simple and effective method to develop functional titanium alloy materials for osteoporotic fracture repair.
Ageing trajectory of the gut microbiota is associated with metabolic diseases in a chronological age-dependent manner
Authors: JingXiang Fu, Wen Qiu, Huimin Zheng, Cancan Qi, Shixian Hu, Wei Wu, Huidi Wang, Guangyan Wu, Peihua Cao, Zhenchao Ma, Chao Zheng, Wen-Jun Ma, Hong-Wei Zhou, Yan He
Journal: Gut (2022)
Quality of life in patients with slowly progressive neuromuscular disorders dependent on mechanical ventilation
Authors: Mathieu Delorme, Christian Reveillere, Christian Devaux, Sandrine Segovia-Kueny, Frédéric Lofaso, Ghilas Boussaid
Journal: Thorax (2022)

This cross-sectional study evaluated health-related quality of life (HRQoL) in patients with slowly progressive neuromuscular disorders dependent on mechanical ventilation (MV; ≥16 hours/day). 119 participants, with 9 years (25th–75th percentiles: 4–15 years) of MV dependence, were included. MV was applied via a tracheostomy in 80 participants (67.2%) and non-invasive interfaces in 39 participants (32.8%), including 28 participants (71.8%) with daytime mouthpiece ventilation. HRQoL was rated good or excellent by 81 participants (68.1%), independently from age, diagnosis or respiratory autonomy. On multivariate analysis, time since MV initiation, independence from family member(s), residence in a rural area, ability to go outdoors with MV and tracheostomy were associated with better HRQoL.
3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
Authors: Ming Zhao, Delong Feng, Longyuan Hu, Lin Liu, Jiali Wu, Zhi Hu, Haojun Long, Qiqi Kuang, Lianlian Ouyang, Qianjin Lu
Journal: Annals of the Rheumatic Diseases (2022)

Three-dimensional (3D) genome alterations can dysregulate gene expression by rewiring physical interactions within chromosomes in a tissue-specific or cell-specific manner and lead to diseases. We aimed to elucidate the 3D genome structure and its role in gene expression networks dysregulated in systemic lupus erythematosus (SLE).We performed Hi-C experiments using CD4+ T cells from 7 patients with SLE and 5 age-matched and sex-matched healthy controls (HCs) combined with RNA sequencing analysis. Further integrative analyses, including transcription factor motif enrichment, SPI1 knockdown and histone modifications (H3K27ac, H3K4me1, H3K4me3), were performed for altered loop-associated gene loci in SLE.We deciphered the 3D chromosome organisation in T cells of patients with SLE and found it was clearly distinct from that of HCs and closely associated with the disease activity of SLE. Importantly, we identified loops within chromosomes associated with the disease activity of SLE and differentially expressed genes and found some key histone modifications close to these loops. Moreover, we demonstrated the contribution of the transcription factor SPI1, whose motif is located in the altered loop in SLE, to the overexpression of interferon pathway gene. In addition, we identified the potential influences of genetic variations in 3D genome alterations in SLE.Our results highlight the 3D genome structure alterations associated with SLE development and provide a foundation for future interrogation of the relationships between chromosome structure and gene expression control in SLE.
SK2 channels set a signalling hub bolstering CAF-triggered tumourigenic processes in pancreatic cancer
Authors: Raphael Rapetti-Mauss, Jérémy Nigri, Camille Berenguier, Pascal Finetti, Sarah Simha Tubiana, Bonnie Labrum, Benoit Allegrini, Bernard Pellissier, Georgios Efthymiou, Zainab Hussain, Corinne Bousquet, Nelson Dusetti, François Bertucci, Hélène Guizouarn, Patricia Melnyk, Franck Borgese, Richard Tomasini, Olivier Soriani
Journal: Gut (2022)

Intercellular communication within pancreatic ductal adenocarcinoma (PDAC) dramatically contributes to metastatic processes. The underlying mechanisms are poorly understood, resulting in a lack of targeted therapy to counteract stromal-induced cancer cell aggressiveness. Here, we investigated whether ion channels, which remain understudied in cancer biology, contribute to intercellular communication in PDAC. We evaluated the effects of conditioned media from patient-derived cancer-associated fibroblasts (CAFs) on electrical features of pancreatic cancer cells (PCC). The molecular mechanisms were deciphered using a combination of electrophysiology, bioinformatics, molecular and biochemistry techniques in cell lines and human samples. An orthotropic mouse model where CAF and PCC were co-injected was used to evaluate tumour growth and metastasis dissemination. Pharmacological studies were carried out in the Pdx1-Cre, Ink4afl/fl LSL-KrasG12D (KICpdx1) mouse model. We report that the K+ channel SK2 expressed in PCC is stimulated by CAF-secreted cues (8.84 vs 2.49 pA/pF) promoting the phosphorylation of the channel through an integrin-epidermal growth factor receptor (EGFR)-AKT (Protein kinase B) axis. SK2 stimulation sets a positive feedback on the signalling pathway, increasing invasiveness in vitro (threefold) and metastasis formation in vivo. The CAF-dependent formation of the signalling hub associating SK2 and AKT requires the sigma-1 receptor chaperone. The pharmacological targeting of Sig-1R abolished CAF-induced activation of SK2, reduced tumour progression and extended the overall survival in mice (11.7 weeks vs 9.5 weeks). We establish a new paradigm in which an ion channel shifts the activation level of a signalling pathway in response to stromal cues, opening a new therapeutic window targeting the formation of ion channel-dependent signalling hubs.
Microbiome variance of the small bowel in Crohn’s disease
Authors: Lucas Wauters, Raul Y Tito, Matthias Ceulemans, An Outtier, Leen Rymenans, Chloë Verspecht, João Sabino, Marc Ferrante, Séverine Vermeire, Tim Vanuytsel, Jeroen Raes
Journal: Gut (2022)